Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry

Research output: Contribution to journalArticle

Abstract

Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.

Details

Authors
  • Linda B Baughn
  • Kathryn Pearce
  • Dirk Larson
  • Mei-Yin Polley
  • Eran Elhaik
  • Michael Baird
  • Colin Colby
  • Joanne Benson
  • Zhuo Li
  • Yan Asmann
  • Terry Therneau
  • James R Cerhan
  • Celine M Vachon
  • A Keith Stewart
  • P Leif Bergsagel
  • Angela Dispenzieri
  • Shaji Kumar
  • S Vincent Rajkumar
External organisations
  • Mayo Clinic Minnesota
  • University of Sheffield
  • DNA Diagnostics Center, Fairfield
  • Mayo Clinic Scottsdale-Phoenix, Arizona
Research areas and keywords

Keywords

  • Adult, African Continental Ancestry Group/genetics, Aged, Aged, 80 and over, Chromosome Aberrations, Chromosome Banding, Disease Progression, Female, Gene Rearrangement, Genes, myc, Genetic Variation, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Odds Ratio, Paraproteinemias/diagnosis
Original languageEnglish
Article number96 (2018)
Number of pages10
JournalBlood Cancer Journal
Volume8
Publication statusPublished - 2018 Oct 10
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes